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Mucosal Clearance of Capsule-Expressing Bacteria Requires Both TLR and Nucleotide-Binding Oligomerization Domain 1 Signaling¹

Tracey A. Zola^*, Elena S. Lysenko^* and Jeffrey N. Weiser^2,*,

^* Department of Microbiology and Department of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104

Expression of capsular polysaccharide by bacterial pathogens is associated with increased resistance to host clearance mechanisms, in particular by evading opsonization and uptake by professional phagocytes. The potential for rapid progression of disease caused by encapsulated bacteria points to the importance of innate immunity at the mucosal surface where infection is initiated. Using a murine model of nasopharyngeal colonization, host immune components that contribute to the mucosal clearance of capsule-expressing bacteria were investigated. Clearance of encapsulated Haemophilus influenzae (Hi) required both TLR and nucleotide-binding oligomerization domain (NOD) signaling pathways, whereas individual deficiencies in each of these signaling cascades did not affect clearance of nonencapsulated strains. Moreover, clearance of Hi-expressing capsular polysaccharide required the recruitment of neutrophils to the site of infection, and ex vivo phagocytic bacterial killing required expression of the NOD1 signaling pathway. Conversely, redundancies within these innate immune pathways of non-neutrophil cells were sufficient to promote mucosal clearance of nonencapsulated Hi. Our findings reveal a role for NOD1 in protection from encapsulated pathogens. In addition, this study provides an example of a microbial virulence determinant that alters the requirements for host signaling to provide effective protection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the U. S. Public Health Service Grants AI44231 and AI38446 to J.N.W. and Center Grant P30 DK50306 from the Molecular Studies of Liver and Digestive Diseases to the Morphology Core of the Center.

² Address correspondence and reprint requests to Dr. Jeffrey N. Weiser, 402A Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104. E-mail address: weiser{at}mail.med.upenn.edu

³ Abbreviations used in this paper: Hi, Haemophilus influenzae; Hib, Hi type b; PRM, pattern recognition molecule; PEC, peritoneal exudate cell; WT, wild type; p, polymeric; p.i., post inoculation.

This article has been cited by other articles:

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